Bacterial Outer Membrane Vesicles: From Discovery to Applications

Abstract

Secretion of cellular components across the plasma membrane is an essential process that enables organisms to interact with their environments. Production of extracellular vesicles in bacteria is a well-documented but poorly understood process. Outer membrane vesicles (OMVs) are produced in gram-negative bacteria by blebbing of the outer membrane. In addition to their roles in pathogenesis, cell-to-cell communication, and stress responses, OMVs play important roles in immunomodulation and the establishment and balance of the gut microbiota. In this review, we discuss the multiple roles of OMVs and the current knowledge of OMV biogenesis. We also discuss the growing and promising biotechnological applications of OMV.

Keywords: OMV; commensalism; outer membrane vesicle; pathogenesis; secretion system; vaccines.

Figure 1

Different roles of outer membrane vesicles in Gram-negative bacteria. Roles of outer membrane vesicles in gram-negative bacteria. OMVs, which are released from the cell envelope, range between 20 and −300 nm and function as a versatile secretion and transport mechanism. OMV roles include intracellular and extracellular communication, quorum sensing, horizontal gene transfer, interbacterial killing, toxin delivery, nutrient hydrolysis, and stress responses.

Figure 2

Mechanisms of OMV production in gram-negative bacteria. (a) Curvature of the OM is induced by the local accumulation of peptidoglycan fragments or misfolded proteins in the periplasm. (b) Removal of proteins anchoring the OM to the underlying peptidoglycan increases OM fluidity, enabling the membrane to bend and form vesicles. (c) Owing to charge repulsion, local enrichment of LPS species with anionic charges induces curvature of the OM and subsequent vesicle formation. Enrichment in deacylated LPS species also promotes membrane curvature because lipid A deacylation changes the shape of LPS from cylinder-like to an inverted cone. (d) The VacJ/Yrb ABC transporter is involved in retrograde transport of phospholipids from the OM. Downregulation of this transporter leads to the accumulation of phospholipids in the outer leaflet of the OM. This causes the outer leaflet to expand rapidly compared to the inner leaflet, which leads to membrane curvature and vesicle formation. (e) Once PQS is produced, it is secreted from the cell and subsequently intercalated into the outer leaflet of the OM owing to its interaction with LPS and phospholipids. Insertion of PQS into the OM causes outer leaflet expansion that increases OMV production. Abbreviations: ABC, ATP-binding cassette; LPS, lipopolysaccharide; OM, outer membrane; OMV, OM vesicle; PQS, Pseudomonas quinolone signal.